To investigate the pathogenicity of a novel MT-ND3 mutation identified in a patient with adult-onset sensorimotor axonal polyneuropathy and report the clinical, morphologic, and biochemical findings.

Clinical assessments and morphologic and biochemical investigations of skeletal muscle and cultured myoblasts from the patient were performed. Whole-genome sequencing (WGS) of DNA from skeletal muscle and Sanger sequencing of mitochondrial DNA (mtDNA) from both skeletal muscle and cultured myoblasts were performed. Heteroplasmic levels of mutated mtDNA in different tissues were quantified by last-cycle hot PCR.

Muscle showed ragged red fibers, paracrystalline inclusions, a significant reduction in complex I (CI) respiratory chain (RC) activity, and decreased adenosine triphosphate (ATP) production for all substrates used by CI. Sanger sequencing of DNA from skeletal muscle detected a unique previously unreported heteroplasmic mutation in mtDNA encoded MT-ND3, coding for a subunit in CI. WGS confirmed the mtDNA mutation but did not detect any other mutation explaining the disease. Cultured myoblasts, however, did not carry the mutation, and RC activity measurements in myoblasts were normal.

We report a case with adult-onset sensorimotor axonal polyneuropathy caused by a novel mtDNA mutation in MT-ND3. Loss of heteroplasmy in blood, cultured fibroblasts and myoblasts from the patient, and normal measurement of RC activity of the myoblasts support pathogenicity of the mutation. These findings highlight the importance of mitochondrial investigations in patients presenting with seemingly idiopathic polyneuropathy, especially if muscle also is affected.

旨在研究在成人发病的感觉运动轴突多发性神经病患者中发现的新型MT-ND3突变的致病性，并报告临床、形态学和生化结果。

对患者的骨骼肌和培养的成肌细胞进行了临床评估以及形态学和生化研究。对骨骼肌 DNA 进行全基因组测序 (WGS)，并对骨骼肌和培养成肌细胞的线粒体 DNA (mtDNA) 进行桑格测序。通过最后一个循环热 PCR 定量不同组织中突变 mtDNA 的异质水平。

肌肉显示出参差不齐的红色纤维、旁晶内含物、复合物 I (CI) 呼吸链 (RC) 活性显着降低，以及 CI 使用的所有底物的三磷酸腺苷 (ATP) 产量减少。对骨骼肌 DNA 进行桑格测序，检测到编码MT-ND3 （编码 CI 中的一个亚基）的 mtDNA 中存在一种以前未报道的独特异质突变。全基因组测序证实了线粒体DNA突变，但没有检测到任何其他可以解释这种疾病的突变。然而，培养的成肌细胞不携带突变，成肌细胞的 RC 活性测量结果正常。

我们报告了一例由MT-ND3中的新型 mtDNA 突变引起的成人发病的感觉运动轴突多发性神经病。血液中异质性的丧失、患者培养的成纤维细胞和成肌细胞以及成肌细胞 RC 活性的正常测量都支持该突变的致病性。这些发现强调了线粒体研究对于看似特发性多发性神经病的患者的重要性，特别是如果肌肉也受到影响的话。